Osteoarthritis (OA) is the most common joint disorder and currently affects >500 million patients worldwide, with ~60% of them also suffering from obesity. The association of OA with Obesity(Ob) is clinically relevant because of the accelerated and relatively more severe pathology compared to idiopathic OA. Chronically unresolved inflammation is a major driver of ObOA-associated tissue damage; resolving this disease-associated inflammation is a viable treatment strategy. In this study, we have encapsulated RvD1 in liposomes and established its efficacy in the mouse model of ObOA at much lower dosages than freely administered RvD1. Liposomal RvD1 (Lipo-RvD1) acted as a source of the RvD1 molecules for ~11 days in vitro in joint fluid derived from patients.From our mice experiments, we observed that Lipo-RvD1 treated joints scored much better compared to untreated and free RvD1 treated joints. Furthermore, our data suggests that, at the cellular level, the Macrophages could be major contributors to the pathology. These results show the potential of lipo-RvD1 as an anti-OA agent.
Current FDA- approved treatments for osteoarthritis (OA) in humans provides solely palliative care, without targeting the underlying degradation. One of the major pathways that mediates tissue damage in OA is chronic unresolved inflammation. Specialized pro-resolution mediators (like Resolvin D1; RvD1) coordinate the resolution at the molecular level. Despite the high potency, RvD1 has a short lifetime in the body. As bioengineers, we generated a novel liposomal formulation to encapsulate RvD1; this formulation protects RvD1 from several deactivating factors. In surgically induced mice model of OA, only Lipo-RvD1 controlled the cartilage damage when administered a month after the surgery, while the free drug was unable to prevent cartilage damage. We found that Lipo-RvD1 functions by damping the proinflammatory activity of synovial macrophages and recruiting a higher number of M2 macrophages at the site of inflammation. Our Lipo-RvD1 formulation was able to target and suppress the formation of the osteophytes and showed analgesic effect, thus emphasizing its ability to treat clinical symptoms of OA. Such controlled-release formulation of RvD1 could represent a patient-compliant treatment for OA.